Malignant Pleural Mesothelioma (MM) is an asbestos-related malignancy which is detected at an advanced stage when curative options are not feasible. Sensitive and specific biomarkers which predict that an asbestos-exposed, high-risk-for-MM individual will develop MM do not exist. By combining the efforts of investigators in the United States and Australia at centers which are known for their expertise in bench work investigations and novel protocols for MM, a multifaceted approach for the rapid discovery and eventual validation of markers of early mesothelial carcinogenesis will be undertaken. This consortium will have the largest collection of reagents for biomarker discovery in MPM in the world, both as archived and prospectively collected specimens. The centers will be linked initially through the refinement of the potential mesothelial biomarker SMRP (soluble members of the mesothelin/Megakaryocyte Potentiating Factor related protein) building on already established industrial collaborations. Preliminary data reveals selective upregulation in sera and pleural effusions of MPM patients compared to other cancers and asbestos exposed individuals. Standards for the normal range of SMRP in asbestos exposed individuals will be established using an already existing >2000 patient Australian serum archive, and the positive/negative predictive value of the ELISA will be determined using existing and prospectively collected sera from MM patients. Both the US and Australian sites will also use the Affymetrix Expression Array Platform to define new soluble biomarkers by comparing non-cancerous mesothelium to early stage, resected mesothelioma tumors from the investigators archives. Preliminary data combining gene expression data with pathway analyses for secreted proteins suggests that osteopontin, MMP-3, and Cartilage Link Protein 1 could be promising markers for the detection of MPM. Further validation of these markers as well as the development of reagents for promising novel biomarkers will be performed at both the US and the Australian sites. [unreadable] [unreadable]